ArticleLaboratory investigation; a journal of technical methods and pathology2015
GDF15 derived from both tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and Erk pathways.
Article in Laboratory investigation; a journal of technical methods and pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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57 citing papers in PubMed, 83 citations in OpenAlex.
- Spatial Atlas of Small Cell Lung Carcinoma Reveals Intratumoral Tumor-State Heterogeneity and an MMP12Cancer science · 2026Article
- Targeting the CAF-GDF15 axis attenuates AKT-mediated mitochondrial rewiring and chemoradiation resistance in esophageal adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- PRSS23 functions downstream of ZEB1 to promote esophageal squamous cell carcinoma progression by driving M2 polarization of tumor associated macrophages.Molecular and cellular biochemistry · 2026Article
- Ectopic expression of GDF15 in cancer-associated fibroblasts enhances melanoma immunosuppression via the GFRAL/RET cascade.Journal for immunotherapy of cancer · 2025Article
- Mapping growth differentiation factor-15 (GDF15)-mediated signaling pathways in cancer: insights into its role across different cancer types.Discover oncology · 2025Article
- Vax-Innate: improving therapeutic cancer vaccines by modulating T cells and the tumour microenvironment.Nature reviews. Immunology · 2025Review
- Personalized bone organoid using iPSC-derived cells for clinically relevant applications.Research square · 2024Article
- Exosomes Derived from Meningitic Escherichia coli-Infected Brain Microvascular Endothelial Cells Facilitate Astrocyte Activation.Molecular neurobiology · 2024Article
- Correlation of Immunomodulatory Cytokines with Tumor Volume and Cerebrospinal Fluid in Vestibular Schwannoma Patients.Cancers · 2024Article
- Macrophages as a Source and Target of GDF-15.International journal of molecular sciences · 2024Review
- scDiffCoAM: A complete framework to identify potential biomarkers for esophageal squamous cell carcinoma using scRNA-Seq data analysis.Journal of biosciences · 2024Article
- GDF15: Immunomodulatory Role in Hepatocellular Carcinoma Pathogenesis and Therapeutic Implications.Journal of hepatocellular carcinoma · 2024Review
- Overexpression of Growth Differentiation Factor 15 in Glioblastoma Stem Cells Promotes Their Radioresistance.Cancers · 2023Article
- Article
- Review
- Knockdown of growth differentiation factor-15 inhibited nonsmall cell lung cancer through inactivating PTEN/PI3K/AKT signaling pathway.Genes & genomics · 2023Article
- GDF15 negatively regulates chemosensitivity via TGFBR2-AKT pathway-dependent metabolism in esophageal squamous cell carcinoma.Frontiers of medicine · 2023Article
- Article
- Multi-omics profiling identifies C1QA/BAnnals of translational medicine · 2022Article
- The Cytokine Growth Differentiation Factor-15 and Skeletal Muscle Health: Portrait of an Emerging Widely Applicable Disease Biomarker.International journal of molecular sciences · 2022Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor-associated macrophages (TAMs) are known to be involved in the progression, angiogenesis, and motility of various cancers. We previously reported the association between an increased number of infiltrating TAMs with tumor progression and poor prognosis in esophageal squamous cell carcinomas (ESCCs). To study the roles of TAMs in ESCC, we first exposed peripheral blood monocyte (PBMo)-derived macrophages from healthy volunteers to conditioned media of TE series human ESCC cell line (TECM) and confirmed the induction of the expression of the M2 macrophage marker CD204 and the protumorigenic factors interleukin (IL)-10, VEGFA, and MMPs. Next, we compared gene expression profiles between PBMo-derived macrophages stimulated with or without TECM by cDNA microarray and focused on growth differentiation factor 15 (GDF15) among the highly expressed genes including IL-6, IL-8, and CXCL1. Our immunohistochemical study of 70 surgically resected ESCCs revealed that GDF15 was present not only in cancer cells but also in macrophages. The high expression of GDF15 in the ESCCs was significantly correlated with several more malignant phenotypes including vessel invasion, lymph node metastasis, and clinical stages. Patients with high GDF15 expression showed significantly poorer disease-free survival (P=0.011) and overall survival (P=0.041). We also found that recombinant human GDF15 promotes cell proliferation and the phosphorylation of both Akt and Erk1/2 in ESCC cell lines in vitro. These results indicate that GDF15 is secreted by both TAMs and cancer cells in the tumor microenvironment and is associated with aberrant growth and a poor prognosis in human ESCC.
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